One of cannabis' most iconic effects is the stimulation of hedonic high-calorie eating-the "munchies"-yet habitual cannabis users are, on average, leaner than non-users. We asked whether this phenotype might result from lasting changes in energy balance established during adolescence, when use of the drug often begins. We found that daily low-dose administration of cannabis' intoxicating constituent, Δ9-tetrahydrocannabinol (THC), to adolescent male mice causes an adult metabolic phenotype characterized by reduced fat mass, increased lean mass and utilization of fat as fuel, partial resistance to diet-induced obesity and dyslipidemia, enhanced thermogenesis, and impaired cold- and β-adrenergic receptor-stimulated lipolysis. Further analyses revealed that this phenotype is associated with molecular anomalies in the adipose organ, including ectopic overexpression of muscle-associated proteins and heightened anabolic processing. Thus, adolescent exposure to THC may promote an enduring "pseudo-lean" state that superficially resembles healthy leanness but might in fact be rooted in adipose organ dysfunction.
Adolescent exposure to low-dose THC disrupts energy balance and adipose organ homeostasis in adulthood / Lin, L.; Jung, K. -M.; Lee, H. -L.; Le, J.; Colleluori, G.; Wood, C.; Palese, F.; Squire, E.; Ramirez, J.; Su, S.; Torrens, A.; Fotio, Y.; Tang, L.; Yu, C.; Yang, Q.; Huang, L.; Dipatrizio, N.; Jang, C.; Cinti, S.; Piomelli, D.. - In: CELL METABOLISM. - ISSN 1932-7420. - 35:7(2023), pp. 1227-1241. [10.1016/j.cmet.2023.05.002]
Adolescent exposure to low-dose THC disrupts energy balance and adipose organ homeostasis in adulthood
Colleluori G.;Cinti S.;
2023-01-01
Abstract
One of cannabis' most iconic effects is the stimulation of hedonic high-calorie eating-the "munchies"-yet habitual cannabis users are, on average, leaner than non-users. We asked whether this phenotype might result from lasting changes in energy balance established during adolescence, when use of the drug often begins. We found that daily low-dose administration of cannabis' intoxicating constituent, Δ9-tetrahydrocannabinol (THC), to adolescent male mice causes an adult metabolic phenotype characterized by reduced fat mass, increased lean mass and utilization of fat as fuel, partial resistance to diet-induced obesity and dyslipidemia, enhanced thermogenesis, and impaired cold- and β-adrenergic receptor-stimulated lipolysis. Further analyses revealed that this phenotype is associated with molecular anomalies in the adipose organ, including ectopic overexpression of muscle-associated proteins and heightened anabolic processing. Thus, adolescent exposure to THC may promote an enduring "pseudo-lean" state that superficially resembles healthy leanness but might in fact be rooted in adipose organ dysfunction.File | Dimensione | Formato | |
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